Epigallocatechin-3-gallate, an active ingredient of Traditional Chinese Medicines, inhibits the 3CLpro activity of SARS-CoV-2

Abstract

SARS-CoV-2 is the etiological agent responsible for the ongoing pandemic of coronavirus disease 2019 (COVID-19). The main protease of SARS-CoV-2, 3CLpro, is an attractive target for antiviral inhibitors due to its indispensable role in viral replication and gene expression of viral proteins. The search of compounds that can effectively inhibit the crucial activity of 3CLpro, which results to interference of the virus life cycle, is now widely pursued. Here, we report that epigallocatechin-3-gallate (EGCG), an active ingredient of Chinese herbal medicine (CHM), is a potent inhibitor of 3CLpro with half-maximum inhibitory concentration (IC50) of 0.874 ± 0.005 μM. In the study, we retrospectively analyzed the clinical data of 123 cases of COVID-19 patients, and found three effective Traditional Chinese Medicines (TCM) prescriptions. Multiple strategies were performed to screen potent inhibitors of SARS-CoV-2 3CLpro from the active ingredients of TCMs, including network pharmacology, molecular docking, surface plasmon resonance (SPR) binding assay and fluorescence resonance energy transfer (FRET)-based inhibition assay. The SPR assay showed good interaction between EGCG and 3CLpro with KD ~6.17 μM, suggesting a relatively high affinity of EGCG with SARS-CoV-2 3CLpro. Our results provide critical insights into the mechanism of action of EGCG as a potential therapeutic agent against COVID-19.

Bioactive Molecules of Tea as Potential Inhibitors for RNA-Dependent RNA Polymerase of SARS-CoV-2

“…These compounds are even effective against Zika, Chikungunya, and Dengue viruses (23). Recent computational and experimental investigations documented the potent antiviral activities of bioactive tea molecules against multiple vital proteins, including the main protease (Mpro), non-structural protein 15 (Nsp15), spike, and RdRp of SARS-CoV-2 (24)(25)(26)(27)(28). The main objectives of the study were to analyze the interaction pattern and binding affinity of selected bioactive molecules and FDA-approved antiviral drugs with the active pocket of SARS-CoV-2 RdRp and, furthermore, to rank and suggest topmost molecules on the basis of their potential to hinder the replication process of SARS-CoV-2.…”

The green tea catechin EGCG provides proof-of-concept for a pan-coronavirus entry inhibitor

“…Alternatively, EGCG is suggested to prevent the binding of HIV glycoprotein 120 to its receptor molecule CD4 on cells [32], and to act as an HIV reverse transcriptase inhibitor [33]. Finally, recent studies have identified in vitro inhibitory effects of EGCG against the SARS-CoV-2 3Clike protease [34][35][36][37]. However, our time-of-addition experiments with HCoV-229E and HCoV-OC43, as well as those of others with SARS-CoV-2 [25], strongly suggest that EGCG predominantly inhibits authentic CoV infection by blocking entry, although other activities might be exerted at higher concentrations.…”

Consumption of Phenolic-Rich Food and Dietary Supplements as a Key Tool in SARS-CoV-19 Infection

“…Additionally, an in silico analysis indicated that these benefits are essentially due to quercetin, kaempferol, luteolin, isorhamnetin, epigallocatechin-3-gallate, naringenin, and wogonin ( Table 2 ). Between these compounds, epigallocatechin-3-gallate was the one with the lowest binding energy (−7.9 kcal/mol), revealing an IC 50 score for 3CL pro (IC 50 = 0.67 ± 0.09 µM) [ 110 ]. To complete the previous study, another metadata analysis of 16 Chinese formulations showed that isorhamnetin has also ability to bind with the ACE2 and 3CL pro , regulating inflammation, cellular processes, and endocrine system [ 111 ].…”